BACKGROUND hTERT contains a high density of minisatellites, of which rare alleles of hTERT-VNTR2-2nd have been reported to be associated with prostate cancer. This shows an association between VNTR and cancer, but this repeat sequence is likely to be associated with genomic instability. Therefore, we investigated the effects of hTERT-VNTR2-2nd on gastrointestinal cancer and the relationship between repeated sequence and chromosome instability. METHODS A case-control study was performed using DNA from 818 cancer-free controls, 539 cases with gastric cancer, 275 cases with colon cancer and 274 cases with rectal cancer. To determine whether minisatellites affect gene expression, expression levels were examined using TERT-reporter vectors in cell lines. In addition, the length of the hTERT-VNTR2-2nd alleles were determined in blood and cancer tissues from 107 gastric cancers, 112 colon cancers and 76 rectal cancers patients to determine whether the repeat sequence was associated with genomic instability during cancer development. RESULTS No statistically significant association between hTERT-VNTR2-2nd and risk of gastrointestinal cancer was detected. However, it has been shown that VNTRs inserted into the enhancer region can regulate the expression of TERT in gastrointestinal cancer cells. Moreover, hTERT-VNTR2-2nd was analyzed in matched blood and cancer tissue from patients with gastrointestinal cancer and in seven among 294 subjects, and hTERT-VNTR2-2nd was found to be rearranged. CONCLUSIONS We suggest that minisatellites are associated with genomic instability in cancer and that the hTERT-VNTRs region may increase hTERT expression in gastrointestinal cancer cells.

中文翻译：

---

hTERT-VNTR2-2nd等位基因参与胃肠道癌的基因组稳定性。

背景技术hTERT包含高密度的小卫星，其中hTERT-VNTR2-2nd的罕见等位基因据报道与前列腺癌有关。这表明VNTR与癌症之间存在关联，但是该重复序列很可能与基因组不稳定有关。因此，我们研究了hTERT-VNTR2-2nd对胃肠道癌的影响以及重复序列与染色体不稳定性之间的关系。方法采用818例无癌对照，539例胃癌，275例结肠癌和274例直肠癌患者的DNA进行病例对照研究。为了确定小卫星是否影响基因表达，使用TERT-报告载体在细胞系中检查了表达水平。此外，确定107例胃癌，112例结肠癌和76例直肠癌患者血液和癌组织中hTERT-VNTR2-2nd等位基因的长度，以确定重复序列是否与癌症发生过程中的基因组不稳定相关。结果未发现hTERT-VNTR2-2nd与胃肠道癌风险之间有统计学意义的关联。然而，已显示插入增强子区域的VNTR可调节胃肠道癌细胞中TERT的表达。此外，在来自胃肠道癌患者的匹配血液和癌组织中以及在294名受试者中的7名中分析了hTERT-VNTR2-2nd，发现hTERT-VNTR2-2nd被重新排列。